The time is now: Achieving FH paediatric screening across Europe – The Prague Declaration

Familial hypercholesterolaemia (FH) is the most common inherited metabolic disorder characterized by high cholesterol and if left untreated leads to premature cardiovascular disease, such as heart attacks. Treatment that begins early in life, particularly in childhood, is highly efficacious in preventing cardiovascular disease and cost-effective, thus early detection of FH is crucial. However, in Europe, less than 10% of people living with FH are diagnosed and even less receive life-saving treatment. The Prague Declaration is a call to action for national and European Union policymakers and decision-makers and a result of the Czech EU Presidency meeting on FH Paediatric Screening (early detection of inherited high cholesterol) at the Czech Senate in Prague on 6th September 2022. It builds on a considerable body of evidence which was discussed at the Technical Meeting under the auspices of the Slovenian EU Presidency in October 2021. The Prague meeting addressed the outstanding barriers to the systematic implementation of FH paediatric screening across Europe. In this article, we present the key points from the Prague meeting and concrete actions needed to move forward.

Political leaders should commit to deliberate and bold efforts to make FH paediatric screening a reality in their country, acknowledging the unequivocal scientific evidence base, cost effectiveness analyses and a (children's) rights' perspective, in the spirit of leaving no-one behind. A multi-stakeholder approach is also needed, to ensure health systems can integrate FH paediatric screening effectively. This includes enablers such as digitalisation, responsible health data sharing, and healthcare professionals (HCPs) education.

Investment and a policy framework for raising awareness of FH amongst medical practitioners and the public, to build trust and responsiveness
National governments in the EU should mobilise significant investment and create appropriate policy guidance to raise awareness amongst the public and healthcare professionals about FH and associated risks, applying the latest knowledge about personalised prevention, behavioural science, health literacy and the social determinants of health. Awareness-raising campaigns and initiatives should be co-created through meaningful engagement of patient organisations, healthcare professionals and citizens.

Comprehensive early detection, screening, diagnosis and life course care programmes in every country
Every country should establish systematic early detection screening and diagnosis for FH, with an appropriate care programme focused on childhood identification and treatment.
The programme should be aligned with the "Best Practices on How to Establish a Screening Programme" [7] and in particular, to those defined by the European Commission's public health best practice portal for FH. Country/region-wide lipid referral centres should coordinate screening and promote family-based care. Lipid referral centres should be guided by the experience of European Reference Networks and the European Atherosclerosis Society Lipid Clinics Network [14]. Each screening programme should incorporate universal, cascade or reverse cascade opportunistic strategies. These may be based initially on cholesterol testing; however, FH genetic testing or ideally a combination of both should be developed as soon as feasible. They should be country/region-specific and in accordance with the organisational structure of respective health care systems.
The screening could occur in the context of regular health care visits (such as vaccinations) or routine healthy children's follow-up, in community settings, or around the perinatal period.

Specific actions to address the barriers to successful large-scale uptake of screening programmes and subsequent treatment
Positive action is needed to ensure the success of screening, including public information campaigns and personalised health advice. It is also important to ensure that a positive diagnosis has no adverse effects on access to treatment for patients and their immediate families. Cost-benefit models should be developed that can be tailored to specific national scenarios to show the longterm cost advantages of FH screening as well as the benefits to individual citizens and their families of early diagnosis.

Targeted R&D to address knowledge gaps
Research to support childhood FH identification should include: • new methods for early identification, diagnosis (including genetic diagnosis), personalised treatments and follow-up; • registries that document FH care, monitor progress in achieving guideline-based treatment goals, and measure health outcomes. These should be developed in the context of the European Health Data Space and the European Reference network and in conjunction with the international FH registry [15]; • long-term clinical trials (3-5 years) and longitudinal studies in children and young people to further assess health outcomes, complications, cost-effectiveness, affordability, and feasibility, that allows full Health Technology Assessments to support decision-making processes; • implementation of science to facilitate guideline-based FH care and assess citizen satisfaction with programmes; • innovation in personalised prevention and treatment in FH; New R&D should be supported through adaption of the appropriate policies.
6. Building the capacity of health professionals and empowering patients on how to best support individuals and families with FH Based on the best available evidence and good practice, capacity-building programmes, and training materials should be created for professionals and individuals, to better deal with the pathology and its burden. Dialogues should take place with patients and healthcare professionals to discuss last advances and evidence.
7. Commitment to shared learning and monitoring through exchange and comparisons beyond borders in-and outside the EU Through funding programmes such as EU4Health, there should be investment in the transferability and uptake of best practice models in FH paediatric screening from other countries, and country level 'score cards' to measure progress according to safety, efficacy, cost and cost-effectiveness, organisational, ethical, legal and social criteria. The experience of FH paediatric screening should be carefully observed and documented for analysis in the context of wider efforts towards better cardiovascular health (CVH) through collaboration with relevant national, European and Global alliances.

Conclusions
We invite national and regional policymakers across the EU, medical societies, patient and public health organisations, and individual experts to support this declaration and to help ensure that FH Paediatric Screening becomes a reality in Europe, as part of European and national strategies to prevent cardiovascular diseases, and to promote cardiovascular health.

Note
The Time is Now: Achieving FH paediatric screening across Europe -The Prague Declaration was endorsed by the following organizations/institutions (see Attachment 1).